COMPANY OVERVIEW DINESH V. PATEL, PHD | PRESIDENT & CEO - FEBRUARY 2022
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COMPANY OVERVIEW
Dinesh V. Patel, PhD | President & CEO
February 2022
1
Forward-looking Statements
This presentation and the accompanying oral presentation contain forward-looking statements made pursuant to the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this presentation, including
statements regarding our future results of operations and financial position, business strategy, product candidates, capital resources, potential markets
for our product candidates, enrollment in our clinical trials, any potential impact on our business related to COVID-19, our potential receipt of milestone
payments and royalties under our Collaboration Agreement with Janssen Biotech, Inc., are forward-looking statements. In some cases, you can identify
forward-looking statements by terminology such as “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potentially”
“predict,” “should,” “will” or the negative of these terms or other similar expressions.
The forward-looking statements made in this presentation involve known and unknown risks, uncertainties and other important factors that may cause
our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by
the forward-looking statements. These forward-looking statements are subject to risks and uncertainties, including those discussed in Protagonist’s
filings with the Securities and Exchange Commission, including in the “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition
and Results of Operations” sections of most recently filed periodic reports on Form 10-K and Form 10-Q and subsequent filings and in the documents
incorporated by reference therein. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be
predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future
events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially
from those projected in the forward-looking statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-
looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.
This presentation concerns products that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug
Administration. They are currently limited by Federal law to investigational use, and no representation is made as to their safety or effectiveness for the
purposes for which they are being investigated. The trademarks included herein are the property of the owners thereof and are used for reference
purposes only. Such use should not be construed as an endorsement of such products. Nothing contained in this presentation is, or should be
construed as, a recommendation, promise or representation by the presenter or Protagonist or any director, employee, agent or advisor of Protagonist.
This presentation does not purport to be all inclusive or to contain all the information you may desire.
2
Protagonist Therapeutics
Peptide-based Medicines
Discovering novel peptide therapeutics through a proprietary technology platform and
developing them to address unmet medical needs in both rare and common diseases
POTENCY
1 Computational 3
Vectrix, Clusters
2
Peptide Chemistry CLINICAL ASSETS
SAR, Leads
Phage Libraries
Hits
Rusfertide
Vectrix ® Clusters
PN-943
STABILITY PN-235
4 6
Systemic Availability
Oral Stability 5 Formulation
Peptidomimetics GI-Restricted SAR, Transport
GI Assays Targeted GI absorption
& delivery
3
Product Portfolio
Addressing Unmet Needs in Multiple Indications with Multi-billion Dollar Market Potential
PROGRAMS CANDIDATE STUDY PHASE 1 PHASE 2 Key Milestones
HEMATOLOGY & BLOOD DISORDERS
VERIFY PV Ph3
Polycythemia Vera (PV) Ph3 initiation
300-11 • Initiation in Q1 2022
REVIVE PV Ph2 PoC • Resuming enrollment
rusfertide 300-04 • Data updates at EHA & ASH 2021
Hepcidin
(PTG-300)
Mimetic
s.c. PACIFIC PV Ph2 in Patients with Elevated Hematocrit • Dosing resumed into OLE
300-08 • Data presented at ASH 2021
• Clinical PoC established
300-06 Hereditary Hemochromatosis (HH) Ph2 PoC
• Data presented at ASH 2021
INFLAMMATORY & IMMUNOMODULATORY DISEASES
Oral GI Restricted • 150 patient study
a4b7-Integrin PN-943 IDEAL Ulcerative Colitis (UC) Ph2 PoC • Enrollment complete
Antagonist • Topline data Q2 2022
Plaque Psoriasis Ph2
Oral • 240 patient study initiated Q1 2022
IL-23R PN-235 FRONTIER 1 Plaque Psoriasis Ph2b PoC initiation
Antagonist IBD Ph2
• Initiation in 2H 2022
4
Rusfertide (PTG-300): Hepcidin Mimetic
To Potentially Address Unmet Needs in Both Rare & Common Diseases
5
Polycythemia Vera
Disease Background
Myeloproliferative neoplasm characterized by
excessive production of red blood cells (RBCs)
Treatment goal
• Characterized by Janus Kinase 2 (JAK2) mutation is to control hematocrit
level
Rusfertide for Polycythemia Vera
Overview of Current Status and Recent Progress
Continued Progress Underway
• Orphan, Fast Track and Breakthrough designations
• Clinical update presented at ASH 2021
• Updated IB and ICF, enhanced safety surveillance measures and inclusion/exclusion criteria following brief (21-day)
clinical hold. Enrollment and dosing have resumed.
• Clinical studies
− Phase 2 REVIVE randomized withdrawal study has resumed enrollment; data updates provided at EHA and ASH 2021
− Phase 2 PACIFIC PV study with elevated hematocrit (48% or higher) has resumed dosing into open-label extension;
data presented at ASH 2021
− Regulatory interactions continue to finalize and enable Phase 3 PERSIST study initiation in Q1 2022; Phase 3 design
presented at ASH 2021
Rusfertide (PTG-300)
• Potential for managing hematocrit per NCCN guidelines without creating iron deficiency, while improving symptoms
• Close consultation underway with regulators
• Natural hormone mimetic therapy for PV
7
Polycythemia Vera
Current Treatment Options
Hydroxyurea Besremi*
Phlebotomy +/- Phlebotomy (ropeginterferon Jakafi
alfa-2b-njft
injection)
• Treatment goal is to maintain HCT ≤ 45% • Recommended when HCT cannot be • Approved for HU resistant/intolerant
• HCT control may be erratic with up and controlled, or in high-risk patients patients
down excursions from 45% • Potential long-term side effects • ~5,300 patients/yr treated**
• Can lead to iron deficiency • Some patients reluctant to use • ~25% develop intolerance or resistance
chemotherapeutic agents • Potential side effects include cytopenia
CHRONIC TREATMENT OVER ~20 YEARS
*Newly FDA approved, undergoing U.S. commercial launch; uncertain place in the therapeutic paradigm at present
**Represents patients treated with Jakafi; uncertain of Besremi population due to recent approval
1. MPN Landmark Survey 2017, Trinity Primary Research 2019 8
Understanding PV Patient Journey
Evaluating the Unmet Need of PV Patients in US
Real world PV patient treatment data
(2018-2019)1
• Evaluation of 28,306 PV patients treated in
2018-2019
• Hematocrit levels: lab tests of 4,264 patients Treated PV Patients
N = 28,306
Key Findings in three categories
>2 HCT
Lab Tests
Treatment Hematocrit Thrombotic risks N= 4,264
patterns management to and events
NCCN guidelines
Representative of treated
PV population
1 Symphony Patient Journey Data Large, representative, and longitudinal source of healthcare claims data that captures over 290MM patients with over 78% of all prescription claims and 60% of all
medical claims. Medical, hospital, and prescription history is captured across treatment settings and payers with history back to 2003 9
Real World PV Patient Treatment Data
Evaluation of 28,306 PV Patients Treated in 2018-19
• Predominant treatment is phlebotomy, regardless of risk
• Hydroxyurea is the most commonly used cytoreductive agent
Treatment • Combination of hydroxyurea and phlebotomy commonly used to control HCT
patterns
• Hematocrit not managed to NCCN guidelines, Only 22% patients had all HCT testsRusfertide: Mechanistic Rationale for Potential Treatment of PV
Polycythemia Vera MOA of rusfertide
FERROPORTIN
transports iron RUSFERTIDE
Elevated Normalized
Hematocrit Hematocrit
Splenic FERROPORTIN
macrophage RBC PRODUCTION
HEPCIDIN EXCESSIVE RBC PRODUCTION
Inhibits
ferroportin 45%
45%
SERUM IRON
serum
iron
Transferrin
delivers iron IRON DELIVERY
11Phase 2 Study of Rusfertide in PV Patients (REVIVE) GOAL: Maintain Hematocrit
Effect of Rusfertide on Phlebotomy Frequency in REVIVE Study
Phlebotomy only (N=31, 49%) Phlebotomy + cytoreductive (N=32, 51%)
Pre-Treatment Treatment Open Label Extension (OLE) Pre-Treatment Treatment Open Label Extension (OLE)
-28 to 0 weeks 28 weeks 52 weeks -28 to 0 weeks 28 weeks 52 weeks
Randomization
Randomization
p< 0.001 p< 0.001
Screening Part 1 – Dose Finding Part 2– Blinded Withdrawal Part 3 – Open Label Extension
Phlebotomy Last dose on study
Data as of September 30, 2021 13Baseline Characteristics of Study Participants in REVIVE Study
Characteristics (n = 63)
AGE THERAPIES
Range 27-76 years (Mean = 56.3 yrs) PHL only 31 (49.2%)
GENDER PHL + HU 18 (28.6%)
Females 18 (28.8%)
PHL + IFN 8 (12.7%)
Males 45 (71.4%)
PHL + RUX 3 (4.8%)
RISK
PHL +Multiple Agents 3 (4.8%)
Low 28 (44.4%)
NUMBER OF PHL IN 28 WEEKS PRIOR
35 (55.6%)
High
[Age based – 36.5%, Thrombotic events – 19.0%] 2-3 15 (23.8%)
DURATION SINCE PV DIAGNOSIS 4-5 33 (52.3%)Rusfertide Controls HCT and Ferritin in REVIVE Study
Hematocrit Ferritin
Screening Part 1 – Dose Finding Part 2/3 – Blinded Withdrawal/OLE Part 3 – Open Label Extension
Box whiskers extend up to 1.5 times interquartile range.
Data as of September 30, 2021 15Improvement in MPN-TSS Scores Following Rusfertide in REVIVE Study
Problems with Concentration
2.0 1.9
Total Symptom Score 1.5
Paried Mean
20 1.0 0.9
16.3
15.2
14.6 0.5
15
11.4
0.0
10 Baseline Week 28
N=24 N=24
5 Worst Level of Fatigue Itching-Pruritus
4 2.5 2.3
3.2
0
3 2.7 2.0
Baseline Week 8 Week 16 Week 28
1.6
N=62 N=56 N=50 N=24
Paired Mean
1.5
Paired Mean
2
1.0
1
0.5
0 0.0
Baseline Week 28 Baseline Week 28
N=24 N=24 N=24 N=24
Data as of September 30, 2021 16Adverse Events Experienced on Rusfertide in REVIVE Study
System Organ Class. - Preferred term AE n (%)
• Most Drug related AEs were Grade 1 or 2
Total number of Subjects 63
• No Grade 4 or 5 Events
No. of subjects with treatment-emergent AE 55 (87)
Blood and Lymphatic Disorders 12 (19.0)
• SAE’s: Syncope, peripheral artery aneurism,
gastroenteritis, chest pain, AML, squamous cell
Anemia 9 (14.3)
carcinoma (skin), melanoma & basal cell
Gastrointestinal disorders 20 (31.7) carcinoma
Nausea 8 (12.7)
• Injection site reaction (ISRs) were most common
Infections and infestations 11 (17.5)
and associated with 28.1% of injections. All ISRs
Metabolism and nutrition disorders 9 (14.3) were transient, and no patient discontinued due
Musculoskeletal and connective tissue disorders 27 (42.9) to ISR.
Nervous system disorders 21 (33.3) • One subject stopped treatment due to AE within
Psychiatric disorders 7 (11.1) 2 weeks (asymptomatic thrombocytosis)
Insomnia 4 (6.3)
• No clinically significant laboratory abnormalities.
Renal and urinary disorders 5 (7.9)
• No Anti Drug Antibody response was noted in
Respiratory 14 (22.2)
any patient
Skin and subcutaneous tissue disorders 23 (36.5)
Pruritis 9 (14.3)
Data as of September 30, 2021 17Conclusions from Phase 2 REVIVE Study
Rusfertide therapy resulted in rapid, sustained and durable hematocrit control without
clinically meaningful changes in white blood cell and platelet counts
Rusfertide demonstrated similar efficacy in all categories of patients, independent of the PV
patient risk category or concurrent therapy with hydroxyurea, interferon or ruxolitinib
Subjects have been treated up to 1.5 years with subjects remaining
essentially phlebotomy-free
Benefits from rusfertide treatment were noted in patient reported outcomes as assessed
by MPN-SAF Total Symptom Score
Results to date suggest that rusfertide is well tolerated; the most common adverse
events were grade 1 or 2
18PACIFIC: Open-Label Phase 2 PV Study in Subjects with high hematocrit (>48%) Patient met the WHO criteria for PV diagnosis and had a baseline hematocrit (HCT) >48%, and a history of ≥3 HCT values >48% in the prior year prior All adult males or females with both high-risk and low-risk criteria treated with phlebotomy alone or with concurrent cytoreductive therapy were enrolled Initial dose: (40 mg SQ twice weekly). After hematocrit was
PACIFIC Phase 2 Study (High Hematocrit)
Therapeutic Phlebotomies Prior to and on Rusfertide
Age/Sex First Dose
005 52/F
004 47/M
006 69/F
007 62/M
011 41/M
008 70/M
009 60/M
001 49/F
Subjects
003 63/M
015 53/F
018 55/M
016 58/M
014 57/M
002 46/M
019 53/M
013 63/M
012 41/M
020 56/M
017 72/F
010 66/M
-52 -48 -44 -40 -36 -32 -28 -24 -20 -16 -12 -8 -4 0 4 8 12 16 20 24 28 32 36 40
Weeks
Screening PTG-300 Dose decision Phlebotomy
Data as of September 30, 2021 20Rusfertide Controls HCT and Reduces RBC Count in PACIFIC Study
Rusfertide Rapidly Controls HCT Rusfertide Rapidly Reduces RBC Count
8
7
RBC (10^6/uL)
6
HCT (%)
5
4
3
N 20 18 17 13 11 9 4 3
Baseline Wk 4 Wk 8 Wk 12 Wk 16 Wk 20 Wk 24 Wk 28
Weeks Weeks
Screening PTG-300 Mean Screening PTG-300 Mean
Data as of September 30, 2021 21Adverse Events in Ongoing PACIFIC Study
System Organ Class All AEs
Preferred term n (%)
Total number of Subjects 20
No. of subjects with treatment-emergent AE 16 (80.0)
Blood and Lymphatic System 3 ( 15.0)
• Most Drug related AEs were Grade 1 or 2
Thrombocytosis 3 ( 15.0)
General disorders and Administration Site Conditions 10 (50.0) • One subject stopped treatment due to AE
Injection Site Erythema 9 (45.0) (Thrombocytosis without bleeding or
Injection Site Induration 5 (25.0) thrombosis; Grade 4 according to
Injection Site Pruritus 2 (10.0) investigator)
Injection Site Swelling 5 (25.0)
• Injection site reaction (ISRs) were most
Pyrexia 2 (10.0)
common and associated with 68% of
Nervous system disorders 5 (25.0)
injections. All ISRs were transient, and no
Headache 2 (10.0)
patient discontinued due to ISR.
Skin and subcutaneous tissue disorders 5 (25.0)
Erythema 4 (20.0) • No anti-drug antibody response was noted in
Pruritus 4 (20.0) any patient
Vascular disorders 2 (10.0)
Hypertension 2 (10.0)
Data as of September 30, 2021 22Conclusions from PACIFIC High Hematocrit Study Rusfertide induction therapy with twice weekly dosing is effective at rapidly achieving target hematocrit below 45% without phlebotomy in all PV patients. Rapid hematocrit control:
Rusfertide Phase 3 PV Study Design (VERIFY Study)
Enrollment Criteria, Primary Endpoint, Key Secondary Endpoints, Additional Assessments
Enrollment Criteria: Primary Endpoint:
• Adult patients with PV per 2016 WHO Criteria • Absence of phlebotomy eligibility based on
• High risk and low risk patients hematocrit control between weeks 20-32
• Patients requiring frequent phlebotomy
• With or without cytoreductive therapy
• Exclusion of patients with invasive cancer in prior 5 years
Additional Assessments:
• Durability of response weeks 32-52
Key Secondary Endpoints:
• Open-label treatment to evaluate long-term
• Number of phlebotomies effects and safety
• Symptom improvement scores
• Safety
The Phase 3 study design capitalizes on the successful outcome of the 60-plus patient open-label Phase 2 REVIVE Study
24Randomized, Double-blind, Placebo-Controlled Phase 3 PV Study (VERIFY)
VERIFY Study of N~250 subjects
Part 1a Part 1b Part 2
Screening Double Blind (Weeks 0-32) Safety
(Up to 4 Durability of Response Long Term Safety Follow-up Follow-up
W eeks) Dose Titration Primary Efficacy (Weeks 32-52) (Weeks 52-156) (4 W eeks)
(Weeks 0-20) (Weeks 20-32)
NDA + MAA filings
Rusfertide + Ongoing Therapy
(n=125)
Screening Rusfertide
+ PV Therapy + Rusfertide
Placebo + Ongoing Therapy Ongoing Therapy
(n=125)
Week 32 Week 52 Week 156
Week 0 Primary Endpoint Durability of End of
Randomize Analysis (Unblind) Response Treatment
(1:1)
The Phase 3 study design capitalizes on the successful outcome of the 60-plus patient open-label Phase 2 REVIVE Study
25PV Commercial Opportunity & Rusfertide Positioning
LOW BURDEN MODERATE BURDEN HIGH BURDEN MF/AML
(Rusfertide Market Preparation: PV Indication
Intend to Demonstrate Clinical & Economic Value Before Approval
Value Distribution Market HEOR Prescriber Competitive Positioning
Proposition Channels Access Education Landscape Strategy
Patients Patient access Pricing & Health Economics & Raise awareness of Existing and future Leader in the
Reimbursement Outcomes Research PV, unmet need and treatments treatment of PV
Prescribers
Strategy for assessing NCCN Guidelines
Payers
economic burden
and benefit of
treatment
27Hereditary Hemochromatosis (HH)
Disease Prevalence and Treatment
HH is predominately due to genetic mutation, leading to a deficiency of hepcidin in the body
Rusfertide, if approved, could serve as a hormone replacement therapy
Excessive iron
Phlebotomy is the
Iron Unmet medical accumulation in
only therapeutic
overload need in specific heart, liver,
option; no
disease subpopulations pancreas, skin,
approved drugs
joint tissues
If untreated, iron overload can cause
hepatomegaly, diabetes mellitus, skin hyperpigmentation, cardiomyopathy, diastolic dysfunction, heart failure, cirrhosis, etc.
Source: Porter JL, Rawla P. Hemochromatosis. (Updated 2020 Jun 18], https://www.ncbi.nlm.nih.gov/books/NBK430862/ 28Proof of Concept Phase 2 Study in Hereditary Hemochromatosis
SCREENING MONTH 1 MONTH 2 MONTH 3 MONTH 4 MONTH 5 MONTH 6
Pre-study
Phlebotomy
and Liver MRI
Adverse event monitoring, dose adjustment, PK and PD (iron parameters)
• Six-month, open-label study in 16 HH patients in maintenance phase of iron depletion
• Stable pre-study phlebotomy for ≥6 months; requiring ≥3 phlebotomies/12 months or ≥4
phlebotomies/15 months
• Patients with end-organ damage or on chelation therapy or erythrocytapheresis were excluded
• Self-administered SC doses once or twice weekly
• Dose adjusted to maintain serum iron & TSATHereditary Hemochromatosis
Summary of Results in HH and Next Steps
• Significantly reduction in number • Maintained liver iron • Lowered serum iron and TSAT
of phlebotomies content
N=14
N=16
0.6PN-943 and IL-23 Receptor Antagonists
Oral Targeted Investigational Therapies for IBD and non-IBD indications
31IBD: Paradigm Shift Toward Targeted Oral and Combination Therapy
A growing multi-billion dollar market
2019: ~ $14B sales1 2029: projected ~ $24B sales 1
Historical IBD Treatment Paradigm Emerging IBD Treatment Paradigm
Injectable mAbs with safer MOAs
• α4β7 integrin: Entyvio® (~ $4B sales 2020)
• IL-12/IL-23: e.g., Stelara®
TNF mAbs dominated IBD Therapy Potential
Oral Targeted Therapy for IBD Future of
• Injectable TNF mAbs – Blockbusters
Protagonist: mAb Validated Pathways IBD
– Humira® & Remicade®
Oral Combo
• Significant room for improvement • PN-9432 (α4β7 integrin)
Therapy
– Low response rates / loss of response • IL-23Rs
– Safety concerns - black box warnings
Other Oral Approaches: New Targets
• S1P1: e.g., Zeposia®
• JAK*: e.g., Xeljanz®, Rinvoq®
*black box warnings
1
GlobalData: Global Drug Forecast and Market Analysis to 2029; 7 Major Markets: US, EU5, JP
2 Investigational product candidate, not approved 32Oral, Gut-Restricted, a4b7-Integrin Peptide Antagonists: PN-943
Fully Owned and Validated Asset and Approach
Clinically Validated, IBD Specific Target
• T cell homing regulated by α4β7 integrin and MAdCAM-1 interaction
• MAdCAM-1 expressed only in GI vasculature
• Entyvio (Vedolizumab) approved for Crohn’s & UC
– ~$5B fiscal 2021 sales
• Superior efficacy for Entyvio vs. Humira in 52 wk Ph3B VARSITY study
Briskin M, et al Am J Pathol. 1997;151:97-110
PN-943: Validated, Gut-restricted Approach
• First-in-class potential as an oral, GI-restricted α4β7-specific antagonist
• PN-943 is ~3x more potent in numerous pre-clinical studies & Ph1 NHV study
vs 1st generation candidate PTG-100 (DDW, 2019)1
– PTG-100 showed signals of clinical efficacy in Ph2a UC trial
(Gastroenterology, 2021)2 Vs.
• PN-943 global Ph2 150 patient study in UC patients in progress
• Study completion anticipated 2Q 2022*
1Mattheakis, 2Sandborn, W. J., Mattheakis, L. C., Modi, N. B., Pugatch, D., Bressler, B., Lee, S., ... & Gupta,
L., Tang, T., Venkataraman, S., Rao, N., Wang, L., Zhao, L., ... & Liu, D.
Y. (2019). The oral α4β7 integrin specific antagonist PN‐10943 is more effective than S. (2021). PTG-100, an oral α4β7 antagonist peptide: preclinical development and phase 1 and
33
PTG‐100 in multiple preclinical studies. Gastroenterology, 156(Suppl 6), S80-S81. 2a studies in ulcerative colitis. Gastroenterology, 161(6), 1853-1864.PN-943: First-in-Class Oral a4b7 Integrin Antagonist
PN-943 superior to first generation PTG-100
• In vitro potency and binding kinetics with similar robust selectivity
• Blood PD effects of local target engagement in 3 species with oral stability and limited blood exposure
• Efficacy in rodent colitis model
PN-943 was advanced into clinical development in 2019
• Oral GI-restricted approach validated by PTG-100 PROPEL Ph2a data
Future Potential Assessed in Surveys with Gastroenterologists
• MEDACorp 2020: “oral anti-integrins were found to be the most exciting unapproved drug class in UC”
• COWEN 2020: The most exciting agent (among 10) in development for moderate-severe IBD was Protagonist’s
PN-943, tied with PTG-200
34PN-943 vs. PTG-100: Blood %RO based Clinical Proof-of-Concept
Ph1 NHV Single Ascending Dose Study
PTG-100 Ph2 UC PoC PN-943 vs PTG-100 Ph1 Data
Ph2A Study PTG-100 Ph1 SAD Ph1 MAD, Day 14
UC 900 mg
44% 96%
Histologic Remission 94%
100 83% 100
(7/16) 74% 80%
74%
16% 80 80
Maximum %RO
74%
Maximum %RO
Clinical Remission* 74%
(3/19)
60 60
40 40
Ph 1 Study PTG-100 20 20
NHVs 1000 mg
0 0
100 mg 300 mg 1000 mg 100 mg 300 mg 1000 mg
% Blood RO 74%
*based on blinded endoscopic re-reads PTG-100 PN-943
* Clinical remission: SFS ≤1, RBS = 0, ESS ≤1
PN-943 vs. PTG-100 Ph1 NHV study
Established 74% blood RO in healthy
subjects as a translational benchmark • Higher effect on blood %RO confirms ~3x superiority of PN-943 vs. PTG-100
– PN-943 300mg blood %RO > PTG-100 1000 mg blood %RO effect
• Saturable target engagement at 1000 mg QD dose
Modi, N. B., Cheng, X., Mattheakis, L., Hwang, C. C., Nawabi, R., Liu, D., & Gupta, S. (2021). Single‐and Multiple‐Dose Pharmacokinetics and Pharmacodynamics of PN‐943, a Gastrointestinal‐Restricted Oral
Peptide Antagonist of α4β7, in Healthy Volunteers. Clinical pharmacology in drug development. 35PTG-100 Ph2A Efficacy Similar to Other IBD Targeted Therapy Drugs
Oral/JAK Oral/S1P1 Injectable Injectable a4b7 integrin
20
a4b7/aEb7 MAdCAM Injectable Oral
18 17.6
16.9
15.8
16 15.2 15.3 15.3
% Patients in Clinical Remission
14
12.3
12 11.6 11.5
11
10 9.6 Active
9
Placebo
8
Delta
6 6.2
6 5.4
4.8
4
2.7
2
0
0
N= 905 234 132 65 81 43 284 73 225 149 19 21
Tofacitinib Ozanimod Etrolizumab SHF-647* Entyvio PTG-100
900 mg q.d.
*Anti-MadCam mAb
* No central read endoscopy (Entyvio) 36IDEAL: PN-943 Phase 2 UC Study
Adult Patients with UC
N≈150 Part-1: Induction Part-2: Extended Treatment Period
Eligibility:
Active Drug 450 mg BID (n=50)
• Moderate – Severe UC
• 3-Component Mayo Score 5-9 points
Randomize
Inclusion: (n=150) Active Drug 150 mg BID (n=50) PN-943
• Bio-naïve and bio-experienced
patients
Placebo BID (n=50)
Primary endpoint:
• Clinical Remission at Week 12
Secondary endpoints: 5 weeks 12 weeks 40 Weeks
Week 52
• Endoscopic, histopath, mucosal
Exploratory endpoints:
• Blood %RO, FCP
Enrollment is complete
Study completion and preliminary data readout anticipated in Q2 2022
37The Outcome of Phase 2 IDEAL study will Inform Phase 3 decisions
• Phase 2 data in UC with various candidates spanning different mechanism of actions
– Large confidence intervals, influenced by study design, duration, size, demographics, & criteria
– Phase 2 outcomes has generally predicted efficacy in Phase 3
Translating HHistorical Ph2, Ph3, and Approval Data in UC 2 ➞ Phase 3 ➞ Approval*
Clinical Remission Delta
Candidate MoA Approval
Phase 2 Phase 3
Vedolizumab (Entyvio®)1 a4b7 integrin 19% 11.5% ✓
Ozanimod (Zeposia®)2 S1P 10% 12.4% ✓
Upadacitinib (Rinvoq®)3 JAK 19.6% 21/29.5% TBD (✓ RA; black box)
*Cross trial comparisons complicated by different inclusion criteria, patient populations, primary endpoint definitions, timing of primary endpoint, phase of clinical development
• Phase 2 data will provide specific guidance for phase 3 program on
– Dose selection
– Powering of registrational primary and secondary endpoints
1. Feagan, B. G., Greenberg, G. R., Wild, G., Fedorak, R. N., Paré, P., McDonald, J. W., ... & Vandervoort, M. K. (2005). Treatment of ulcerative colitis with a humanized antibody to the α4β7 integrin. New England Journal of Medicine, 352(24), 2499-
2507; Feagan, B. G., Rutgeerts, P., Sands, B. E., Hanauer, S., Colombel, J. F., Sandborn, W. J., ... & Parikh, A. (2013). Vedolizumab as induction and maintenance therapy for ulcerative colitis. New England Journal of Medicine, 369(8), 699-710.
2. Sandborn, W. J., Feagan, B. G., Wolf, D. C., D’Haens, G., Vermeire, S., Hanauer, S. B., ... & Olson, A. (2016). Ozanimod induction and maintenance treatment for ulcerative colitis. New England Journal of Medicine, 374(18), 1754-1762; Sandborn,
W. J., Feagan, B. G., D’Haens, G., Wolf, D. C., Jovanovic, I., Hanauer, S. B., ... & Danese, S. (2021). Ozanimod as induction and maintenance therapy for ulcerative colitis. New England Journal of Medicine, 385(14), 1280-1291.
3. Danese, S., Vermeire, S., Zhou, W., Pangan, A., Siffledeen, J., Hébuterne, X., ... & Pannaccione, R. (2021). OP24 Efficacy and safety of upadacitinib induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from the
phase 3 U-ACHIEVE study. Journal of Crohn's and Colitis, 15(Supplement_1), S022-S024.; Vermeire, S., Danese, S., Zhou, W., Pangan, A., Greenbloom, S., D’Haens, G., ... & Panaccione, R. (2021). OP23 Efficacy and safety of upadacitinib as
induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from phase 3 U-ACCOMPLISH study. Journal of Crohn's & Colitis, 15(Suppl 1), S021.
38Oral, IL-23 Receptor Specific Peptide Antagonist: PN-235
Janssen Partnership
p19 antibody: Stelara®: Blocks both
Objective Blocks IL-23 pathway IL-23 & IL-12 pathways
• Extend the Stelara® franchise and transition from injectable to oral
p19 p40 p35 p40
targeted therapy IL-23R Antagonist:
Blocks IL-23 receptor
– Stelara approved for psoriasis, psoriatic arthritis, Crohn’s, UC & IL-23 pathway
IL-12Rβ1
IL-12Rβ1
IL-12Rβ2
IL-23R
Terms CELL MEMBRANE
• May 2017: Partnership initiated
• $87.5M in upfront and development milestones received to date
IL-23 IL-12
• Eligible for about additional $900M in milestones, up to double digit
royalties, US co-detailing rights
− Study initiation milestones: $25M (psoriasis) and $10M (IBD)
Status Stelara® is a key Janssen franchise
• Focus on the PN-235 candidate, with its superior potency and PK/PD • ~$7.7B total global sales in 2020
profile, for IBD and non-IBD indications
– PN-235 (JNJ-77242113): Ph1 completed in 2021; advancing in
psoriasis indication in FRONTIER 1 study, initiated in early 2022, and Vs.
in IBD indications in 2H 2022
39Janssen FRONTIER 1 Phase 2b Plaque Psoriasis (PsO) Study
Screening Treatment Safety Follow-up Week 156
Adult Patients with PP End of
(Up to 4 Weeks)* (Weeks 0-16) (4 Weeks)
N≈240 Treatment
Eligibility:
Dose 1 QD
• Moderate – Severe PP
PN-943
Inclusion:
Dose 2 QD
• BSA > 10%
Randomize
• PASI > 12
Dose 3 QD
Primary endpoint: Safety Follow-up
• PASI > 75 at Week 16 Dose 1 BID
Dose 3 BID
Placebo
Week 0 Week 16
Randomize Primary Endpoint
$25M milestone payment when third patient is dosed
40PROTAGONIST THERAPEUTICS
Protagonist Team and Financials
41
41Protagonist Team
Experience & Expertise in Drug Discovery, Clinical Development, and Commercialization
Dinesh Patel, PhD President & CEO
David Liu, PhD CSO, Head of Discovery & Pre-Clinical Dev
Samuel Saks, MD Clinical Development Advisor
Suneel Gupta, PhD Chief Development Officer
Donald Kalkofen Chief Financial Officer
Tracy Woody EVP, Commercial Strategy
Matthew Gosling, JD EVP, General Counsel
Mohammad Masjedizadeh, PhD EVP, Chief Technical Officer
Scott Plevy, MD EVP & Therapeutic Head, Gastroenterology
Ashok Bhandari, PhD SVP, Discovery Chem & Process Res
Paula O’Connor, MD SVP, Clinical Development
Abha Bommireddi, MS SVP, Program Management
Carter King, MBA SVP, Business Development
Nishit Modi. PhD, MBA SVP, Clinical Pharmacology
Sarita Khanna, PhD SVP, Biometrics
42Financial Highlights
Financial resources forecast extends through full year 2024
$352.5M 2024 47.7M
CASH & SECURITIES CASH & SECURITIES SHARES OUTSTANDING
As of September 30, 2021 provide financial resources as of September 30, 2021
forecast through full year 2024*
*This includes our initial CMC investments in preparation for a phase 3 with PN-943 in UC, should we achieve positive Phase 2
results, we will be in a position to share more on any next steps after the data read out for PN-943 in Q2 2022 43Upcoming Catalysts in 2022 and Beyond
Significant opportunities to unlock and capture value in the 12-24 months ahead
Anticipated Events of 2022
Products 2023
Q1 Q2 Q3 Q4
Rusfertide • VERIFY: Ph3 250 patient • Ph3 enrollment
1 PV study initiation ASH completion (1H)
• REVIVE: Ph2 PV study EHA • Ph2 randomization
2 (300-04) continuation results (Q1)
3 • 2nd indication: HH market opportunity and next steps
PN-943 • IDEAL: Ph2 150 • Ph3 UC study
4 patient UC study initiation*
topline results *assuming positive Ph2 data
PN-235 • Ph2 initiation – Plaque • Ph2 plaque psoriasis
5 psoriasis 6 • Ph2 initiation in IBD (2H) study results
• $25M milestone • $10M milestone
7
Discovery • Nomination of oral hepcidin mimetic candidate
8
Pre-Clinical • Nomination of new development candidate – new target for new indication(s)
44THANK YOU
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